Chromosome Anomalies and Disorders

Mitosis & Meiosis

• Mitosis consists of a cell cycle with G1, S, and G2 phases; interphase precedes division.
• G1 phase contains one diploid cell; in the S phase, DNA is duplicated forming two sister chromatids.
• G2 phase prepares chromosomes for condensation; two daughter cells produced carry equal genetic information.
• Mitosis phases include:
  • Prophase: Mitotic spindle forms, centrosomes pair.
  • Prometaphase: Nuclear membrane dissolves, chromosomes attach to spindle microtubules.
  • Metaphase: Chromosomes align at the equator.
  • Anaphase: Sister chromatids separate at centromeres.
  • Telophase: Chromosomes de-condense, nuclear membranes reform.

Non-disjunction and its Impact on Meiosis

• Non-disjunction refers to the failure of chromosomes to separate properly during meiosis.
• This leads to aneuploidy, the presence of an abnormal number of chromosomes in a cell.
• Non-disjunction can occur in:
  • Meiosis I: Leads to four unbalanced gametes.
  • Meiosis II: Results in two normal and two unbalanced gametes.
• Resultant gametes can produce monosomic (missing one chromosome) or trisomic (extra chromosome) offspring.

Classifications of Chromosomal Abnormalities

• Chromosomal anomalies can be classified into numerical and structural abnormalities.
• Numerical abnormalities alter complete haploid sets (n) of chromosomes.
• Structural abnormalities affect chromosome structure and organization.

Numerical Chromosomal Anomalies

• Down Syndrome (Trisomy 21):

  • Karyotype: 47, XY, +21.
  • Most cases result from maternal non-disjunction; incidence rises with maternal age.
  • Symptoms: Facial dysmorphology, intellectual disability (IQ < 50).

• Edward's Syndrome (Trisomy 18):

  • Karyotype: 47, XY, +18.
  • Occurs in approximately 1 in 6,000 live births; high mortality in infancy.
  • Common anomalies: Heart defects, kidney malformations.

• Patau Syndrome (Trisomy 13):

  • Karyotype: 47, XY, +13.
  • Half of affected individuals die within the first month; limited survival beyond one year.
  • Presents multiple dysmorphic features.

Numerical Sex Chromosome Anomalies

• Turner's Syndrome (Monosomy X):

  • Karyotype: 45,XO; occurs in 1 in 4,000 females.
  • The only viable monosomy; traits include short stature and webbed neck.

• Klinefelter Syndrome:

  • Karyotype: 47, XXY; affects about 1 in 600 males.
  • Results from nondisjunction during maternal meiosis I; symptoms include breast enlargement and sterility.

Mosaicism

• Defined as the presence of genetically distinct cell lines derived from a single zygote.
• Denoted in karyotypes (e.g., 46, XY / 47, XY, +21).
• Caused by mitotic non-disjunction; not to be confused with chimerism (from multiple zygotes).

Structural Chromosomal Anomalies

• Reciprocal Translocation:

  • Involves exchange between two non-homologous chromosomes (e.g., Philadelphia chromosome linked to CML).

• Robertsonian Translocation:

  • Loss of short arms from acrocentric chromosomes, resulting in fusion of long arms; carriers have 45 chromosomes.

• Deletion:

  • Refers to the loss of chromosome segments; indicated as "del" in nomenclature.

• Inversion:

  • Involves segments breaking and rejoining; categorized as pericentric or paracentric.

• Isochromosome:

  • Occurs when centromeres divide transversely, resulting in chromosome duplication along one arm.

• Ring Chromosome:

  • Formed when breaks on each arm reunite as a ring structure; often unstable in mitosis.

Take Home Message

• Chromosome abnormalities can be classified into numerical and structural, impacting genetic stability.
• Normal meiosis results in four haploid gametes; non-disjunction leads to trisomy or monosomy.
• Mosaicism arises from a single zygote; chimerism from fusion of multiple zygotes.
• Structural abnormalities include various rearrangements, each affecting genetic expression differently.